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HSP90AB1 is a molecular chaperone. Chaperones are proteins that bind to other proteins, thereby stabilizing them[4][5][6][7][8][9][10] in an ATP-dependent manner.[11] Chaperones stabilize new proteins during translation, mature proteins which are partially unstable but also proteins that have become partially denatured due to various kinds of cellular stress. In case proper folding or refolding is impossible, HSPs mediate protein degradation. In addition, they have also specialized functions, such as intracellular transport into organelles.

C-terminal domain (CTD) which is the dimerization domain (base of the V).

Between these domains, there are short charged domains. Co-chaperones primarily bind to the NTD and CTD. The latter Co-chaperones usually contain a tetratricopeptide repeat (TPR) domain which binds to a MEEVD motif at the C-terminus of the HSP.[17][27] Inhibition of HSP90 activity by geldanamycin derivatives is based on their binding to the ATP binding site.[11]

Cystic fibrosis (CF, mucoviscidosis) is a genetic disease with increased viscosity of various secretions leading to organ failure of lung, pancreas and other organs. It is caused in nearly all cases by a deletion of phenylalanine 508 of CFTR (cystic fibrosis transmembrane conductance regulator). This mutation causes a maturation defect of this ion channel protein with increased degradation, mediated by HSPs. Deletion of the co-chaperone AHA1 (activator of heat shock 90kDa protein ATPase homolog 1) leads to stabilization of CFTR and opens up a perspective for a new therapy.[33]

HSP90AB1 and its co-chaperones are frequently overexpressed in cancer cells.[34] They are able to stabilize mutant proteins thereby allowing survival and increased proliferation of cancer cells. This renders HSPs potential targets for cancer treatment.[35][36][37] In salivary gland tumors, expression of HSP90AA1 and HSP90AB1 correlates with malignancy, proliferation and metastasis.[38] The same is basically true for lung cancers where a correlation with survival was found.[39]